Dengue Structure Differs at the Temperatures of Its Human and Mosquito Hosts

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 Apr 10

PMID 23569243

Citations 115

Authors

Xinzheng Zhang

Ju Sheng

Pavel Plevka

Richard J Kuhn

Michael S Diamond

Michael G Rossmann

Affiliations

Soon will be listed here.

Abstract

We report on a conformational transition of dengue virus when changing the temperature from that present in its mosquito vectors to that of its human host. Using cryoelectron microscopy, we show that although the virus has a smooth surface, a diameter of ∼500 Å, and little exposed membrane at room temperature, the virions have a bumpy appearance with a diameter of ∼550 Å and some exposed membrane at 37 °C. The bumpy structure at 37 °C was found to be similar to the previously predicted structure of an intermediate between the smooth mature and fusogenic forms. As humans have a body temperature of 37 °C, the bumpy form of the virus would be the form present in humans. Thus, optimal dengue virus vaccines should induce antibodies that preferentially recognize epitopes exposed on the bumpy form of the virus.

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References

Halstead S . Dengue vaccine development: a 75% solution?. Lancet. 2012; 380(9853):1535-6. DOI: 10.1016/S0140-6736(12)61510-4. View

Tang G, Peng L, Baldwin P, Mann D, Jiang W, Rees I . EMAN2: an extensible image processing suite for electron microscopy. J Struct Biol. 2006; 157(1):38-46. DOI: 10.1016/j.jsb.2006.05.009. View

Teoh E, Kukkaro P, Teo E, Lim A, Tan T, Yip A . The structural basis for serotype-specific neutralization of dengue virus by a human antibody. Sci Transl Med. 2012; 4(139):139ra83. DOI: 10.1126/scitranslmed.3003888. View

Hung J, Hsieh M, Young M, Kao C, King C, Chang W . An external loop region of domain III of dengue virus type 2 envelope protein is involved in serotype-specific binding to mosquito but not mammalian cells. J Virol. 2003; 78(1):378-88. PMC: 303388. DOI: 10.1128/jvi.78.1.378-388.2004. View

Crill W, Roehrig J . Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells. J Virol. 2001; 75(16):7769-73. PMC: 115016. DOI: 10.1128/JVI.75.16.7769-7773.2001. View

Zhang Y, Zhang W, Ogata S, Clements D, Strauss J, Baker T . Conformational changes of the flavivirus E glycoprotein. Structure. 2004; 12(9):1607-18. PMC: 4152830. DOI: 10.1016/j.str.2004.06.019. View

Dowd K, Jost C, Durbin A, Whitehead S, Pierson T . A dynamic landscape for antibody binding modulates antibody-mediated neutralization of West Nile virus. PLoS Pathog. 2011; 7(6):e1002111. PMC: 3128118. DOI: 10.1371/journal.ppat.1002111. View

Kaufmann B, Vogt M, Goudsmit J, Holdaway H, Aksyuk A, Chipman P . Neutralization of West Nile virus by cross-linking of its surface proteins with Fab fragments of the human monoclonal antibody CR4354. Proc Natl Acad Sci U S A. 2010; 107(44):18950-5. PMC: 2973864. DOI: 10.1073/pnas.1011036107. View

Sabchareon A, Wallace D, Sirivichayakul C, Limkittikul K, Chanthavanich P, Suvannadabba S . Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet. 2012; 380(9853):1559-67. DOI: 10.1016/S0140-6736(12)61428-7. View

10.

van der Schaar H, Rust M, Chen C, van der Ende-Metselaar H, Wilschut J, Zhuang X . Dissecting the cell entry pathway of dengue virus by single-particle tracking in living cells. PLoS Pathog. 2008; 4(12):e1000244. PMC: 2592694. DOI: 10.1371/journal.ppat.1000244. View

11.

Bressanelli S, Stiasny K, Allison S, Stura E, Duquerroy S, Lescar J . Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation. EMBO J. 2004; 23(4):728-38. PMC: 380989. DOI: 10.1038/sj.emboj.7600064. View

12.

Butrapet S, Huang C, Pierro D, Bhamarapravati N, Gubler D, Kinney R . Attenuation markers of a candidate dengue type 2 vaccine virus, strain 16681 (PDK-53), are defined by mutations in the 5' noncoding region and nonstructural proteins 1 and 3. J Virol. 2000; 74(7):3011-9. PMC: 111799. DOI: 10.1128/jvi.74.7.3011-3019.2000. View

13.

Kuhn R, Zhang W, Rossmann M, Pletnev S, Corver J, Lenches E . Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell. 2002; 108(5):717-25. PMC: 4152842. DOI: 10.1016/s0092-8674(02)00660-8. View

14.

Yu I, Zhang W, Holdaway H, Li L, Kostyuchenko V, Chipman P . Structure of the immature dengue virus at low pH primes proteolytic maturation. Science. 2008; 319(5871):1834-7. DOI: 10.1126/science.1153264. View

15.

Li L, Lok S, Yu I, Zhang Y, Kuhn R, Chen J . The flavivirus precursor membrane-envelope protein complex: structure and maturation. Science. 2008; 319(5871):1830-4. DOI: 10.1126/science.1153263. View

16.

Halstead S . Dengue. Lancet. 2007; 370(9599):1644-52. DOI: 10.1016/S0140-6736(07)61687-0. View

17.

Cherrier M, Kaufmann B, Nybakken G, Lok S, Warren J, Chen B . Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody. EMBO J. 2009; 28(20):3269-76. PMC: 2771083. DOI: 10.1038/emboj.2009.245. View

18.

Ludtke S, Baldwin P, Chiu W . EMAN: semiautomated software for high-resolution single-particle reconstructions. J Struct Biol. 1999; 128(1):82-97. DOI: 10.1006/jsbi.1999.4174. View

19.

Zhang W, Chipman P, Corver J, Johnson P, Zhang Y, Mukhopadhyay S . Visualization of membrane protein domains by cryo-electron microscopy of dengue virus. Nat Struct Biol. 2003; 10(11):907-12. PMC: 4148076. DOI: 10.1038/nsb990. View

20.

Rossmann M, Bernal R, Pletnev S . Combining electron microscopic with x-ray crystallographic structures. J Struct Biol. 2002; 136(3):190-200. DOI: 10.1006/jsbi.2002.4435. View